Liquid or semi-liquid biomaterials that can be delivered in the human body, either by open surgical, direct percutaneous puncture, or remote endovascular access, constitute an important component of the modern therapeutic armentarium. Some of these agents, such as the acrylic bone cements, have been in clinical use for a long period of time, while others are currently reaching the last stages of preclinical development. The recent advent of minimally invasive vascular and non-vascular therapeutic techniques has given a new impetus for the development of such agents. The treatment of cerebral aneurysms with liquid embolic agents represents a good illustration of the potential advantages offered by these types of materials. However, there remain challenges that need to be addressed before clinical application may be recommended.
The goal of endovascular treatment of aneurysms is to obtain a complete and permanent exclusion of the aneurysmal sac from the arterial circulation, while preserving the patency of the parent vessel. Ideally, aneurysm thrombosis followed by endothelialization across the aneurysm orifice should be obtained. Detachable microcoils represent the currently accepted minimally invasive alternative to conventional surgical clipping for the treatment of cerebral aneurysms; however, even when an aneurysm filled with microcoils appears radiographically densely packed, typically less than half of the cavity volume is occupied by the microcoil mass. The remainder of the aneurysmal cavity is, in fact, filled with thrombus, which may or may not become organized.
Liquid embolic agents are emerging as promising alternatives to more homogeneous aneurysm filling, and the decreased recurrence rates seen; however, animal studies and preliminary human experience using various agents have revealed significant limitations inherent to the use of liquid embolic agents, including migration of the agent, parent artery occlusion, catheter adhesion, and cytotoxicity.
A potential alternative is alginate-based liquid embolic agents. Alginate is highly biocompatible, and its delivery and hardening can be controlled. However, complications may arise from the use of alginate. For instance, in some cases alginate hydrogel has been found to protrude out of the neck of the aneurysm and migrate into the parent artery during injection, a situation that carries a high risk of major complication such as vessel occlusion and stroke. Similar complications may result from the use of alginate in other therapeutic indications, such as in inadvertent obliteration of a normal cerebral artery during the embolization of a vascular malformation. Thus, there remains a need in the art for the development of agent(s) that can selectively dissolve alginate. Such a new agents would fill an urgent need in many different applications, such as embolization procedures, and cosmetic and reconstructive procedures. These agents would increase the safety of current therapy, and further provide potential use in a variety of clinical and experimental applications.